Synchronous mantle cell lymphoma and lung adenocarcinoma presenting in a pleural effusion: A rare tumour combination and a potential pitfall of cytodiagnosis

Dear Editor, Mantle cell lymphoma (MCL) is a B-cell neoplasm that is generally composed of monomorphic small to medium lymphoid cells, and is characterised by chromosomal translocation t (11;14) (q13;q32) and cyclin D1 overexpression. MCL represents about 4% of all lymphomas in the USA, 7%-9% in Europe and 3% in Japan. The synchronous occurrence of MCL and other malignancies is extremely rare. We could find only four reports of synchronous MCL and lung cancer (adenocarcinoma, squamous cell carcinoma, small cell carcinoma and undifferentiated carcinoma). However, these previous reports did not include cytological findings. Therefore, cytological findings of MCL coexistent with other malignant cells in the same specimen have not been reported. We herein report a case of MCL that synchronously appeared with lung adenocarcinoma cells in pleural effusion. Our experience may suggest a pitfall of the cytodiagnosis of MCL. A 71-year-old Japanese man visited a nearby hospital due to abdominal distension. Computed tomography (CT) revealed systemic bulky lymph node swelling, ascites, bilateral pleural effusion and a mass lesion measuring 22 mm in diameter at the upper lobe of the left lung (Figure 1A,B). The patient was transmitted to our hospital for further examination and treatment. Laboratory tests on admission revealed anaemia (red blood cell count, 3.41 9 10/L; haemoglobin concentration, 8.2 g/dL) and an inflammatory reaction (white blood cell count, 10.7 9 10/L; C-reactive protein, 11.83 mg/dL). The serum soluble interleukin-2 receptor level was markedly elevated (12259 U/mL). Aspirations of the left pleural effusion and bone marrow were also performed on the day of admission and submitted for cytological and pathological examination, respectively. The cytological specimen of the left pleural effusion showed many clusters of atypical cells with irregularly shaped nuclei with prominent nucleoli that showed epithelial cell adhesion and a piledup structure in the background of many lymphocytes (Figure 1C). Therefore, an initial cytodiagnosis of adenocarcinoma was made. We were not aware of the cytological atypia of background lymphocytes at the time of the initial diagnosis. A clinician who received the cytological report contacted us to discuss whether there were cytological findings suggesting lymphoma, as malignant lymphoma had been suspected clinically. We therefore performed an intensive re-examination of the cytology, especially in the Giemsa-stained specimens. Most of the lymphocytes that appeared in the background of the adenocarcinoma cells were smallto medium, the nuclei were irregularly shaped and sometimes constricted, and the chromatin pattern was reticular and unequally distributed. Therefore, we strongly suspected that these atypical lymphocytes were lymphoma cells. At almost the same time, histopathological examination of a bone marrow clot revealed massive infiltration of MCL cells showing immunophenotypes of CD20+, CD79a+, CD10-, bcl-6-, bcl-2+, CD5+ and cyclin D1+ in the immunohistochemistry. We asked the clinician to resubmit the pleural effusion for a definitive cytodiagnosis. We made a cell block from the resubmitted left pleural effusion in addition to routine Papanicolaouand Giemsa-stained specimens. Clusters of adenocarcinoma cells and atypical lymphocytes were also observed in the Papanicolaouand Giemsa-stained specimens (Figure 2A,B). Many reactive lymphocytes, macrophages and mesothelial cells were also intermingled. The cytoplasmic expression of cytokeratin 7 and the nuclear expression of TTF-1 in adenocarcinoma cells and the expressions of CD5 and cyclin D1 in atypical lymphocytes were confirmed by immunohistochemical analysis of the cell block (Figure 2C,D). Thus, a final cytological diagnosis of coexisting MCL and lung adenocarcinoma was made. Infiltration of MCL was also confirmed at the right pleural effusion, although adenocarcinoma cells were not observed. Lymph node biopsy was not performed because a definite diagnosis of MCL was already obtained and the patient’s general condition was worsening. Because of the lack of reliable evidence, the therapeutic strategy in the present case was a matter of debate. Therefore, the cancer board of Saga University Hospital held a meeting to discuss the optimal strategy. Although both tumours were stage IV by TNM classification, the patient was considered to be falling into multiple organ failure due to the progression of MCL, while the lung adenocarcinoma was restricted to the left thoracic cavity. Therefore, it was decided that the treatment for MCL should precede the treatment for lung adenocarcinoma. The patient underwent treatment with cyclophosphamide, doxorubicin, vincristine and prednisone and then was treated with rituximab and bendamustine. Although a reduction of lymph node swelling was observed, the patient died of septic shock almost 3 months after hospitalisation. An autopsy was not permitted. We have presented the first reported case of MCL appearing synchronously with adenocarcinoma cells in pleural effusion. In this case, we did not initially notice MCL cells in the cytological specimens, probably for the following reasons. First, our attention was Accepted: 13 December 2017